Acta Neurochir (2000) [Suppl] 76: 343-345 © Springer-Verlag 2000 Protective Effect of a Novel Vitamin E Derivative on Experimental Traumatic Brain Edema in Rats - Preliminary Study Y. Ikeda 1 , Y. Mochizuki 1 , Y. Nakamura 1 , K. Dohi 1 , H. Matsumoto 1 , H. Jimbo 1 , M. HayashP, K. Matsumoto 1 , T. Yoshikawa 2 , H. Murase\ andK. Sato 4 1 Department of Neurosurgery, Showa University School of Medicine, Tokyo 2 Department of Medicine, Kyoto Prefectual University of Medicine, Kyoto, Japan 3 CCI Co., Gifu, Japan 4 Analysis Center, School ofPharrnaceutical Sciences, Showa University, Tokyo, Japan Summary Oxygen free radicals have been proposed to be one of the major mechanisms of secondary brain damage in traumatic brain injury. Protective effect by vitamin E against oxidative damage has at- tracted much attention. Recent studies have demonstrated a novel vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5, 7,8- tetramethylchroman-6-ol (TMG), has excellent water-solubility and antioxidant activity. The purpose of this study was to investigate protective effects of TMG on experimental traumatic brain edema (BE). Male Wistar rats were anaesthetized with chloral hydrate. Traumatic BE was produced by a cortical freezing lesion. Animals were separated into three groups: saline-treated rats (n = 4), TMG- treated (4 mg/kg) rats (n = 7) and TMG-treated (40 mg/kg) rats (n = 8). Saline or TMG was administered intravenously before lesion production. Animals were sacrificed at 6 hours after lesion production and the brain water content was determined by the dry- wet weight method. Half-life ofTMG after intravenous administra- tion of TMG was also investigated. The half life of TMG was ap- proximately 5 minutes. TMG (40 mg/kg) significantly attenuated BE following cryogenic brain injury (p < 0.01). In conclusion, this preliminary study has demonstrated that a novel vitamin E deriva- tive might be promising in the treatment of traumatic BE. Keywords: Brain edema; brain injury; vitamin E; free radicals. Introduction Oxygen free radicals have been proposed to be one of the major mechanisms of secondary brain damage in traumatic brain injury [1]. Lipid peroxidation through oxygen free radicals is recognized as an im- portant pathological process. Protective effect by vita- min E against oxidative damage has attracted much attention [2, 3]. It has been reported that vitamin E scavenges not only peroxyl radicals but also singlet oxygen and the superoxide radical [4-6]. Since the mobility of vitamin E in the biological membranes is restricted due to its long phytyl side chain, it seems unlikely to scavenge active oxygens which might be generated in the aqueous phase. Recent studies [7, 8] have demonstrated that a novel vitamin E derivative, 2-( alpha-D-glucopyranosyl)methyl-2,5, 7 ,8- tetramethylchroman-6-ol(TMG), has excellent water- solubility and antioxidant activity (Fig. 1). The purpose of this study was to investigate protec- tive effects of TMG on experimental traumatic brain edema (BE). Materials and Methods Measurement of Superoxide Scavenging Activity of TMG Determination of superoxide scavenging activity of TMG was performed by electron spin resonance spectrometry using 5,5- dimethyl-l-pyrroline-l-oxide (DMPO) as a spin trap. Fifty micro- liters of 2 mM hypoxanthine, 20 IJl of 0.5 mM diethylenetriamine- pentaacetic acid (DETAPAC), 50 IJl ofTMG, 50 IJl ofDMPO and 30 of xanthine oxidase were put into a test tube and mixed by an automatic mixer. Then the solution was placed in a special flat cell and DMPO-0 2 , spin adduct was analyzed by electron spin reso- nance spectrometry. Surgical Procedure and Experimental Protocols Male Wistar rats, weighing 250 to 300 g each, were anesthetized intraperitoneally with chloral hydrate (360 mg/kg). A midline scalp incision and a craniectomy were made in the right parietal region. Cortical cryogenic injury was produced by application of a metal probe cooled by dry ice to the dura of the right parietal region. The dura was left intact. The skin was closed with sutures. Animals were separated into three groups: saline-treated rats with lesion produc- tion (n = 4), TMG-treated (4 mg/kg) rats with lesion production (n = 7) and TMG-treated (40 mg/kg) rats with lesion production